Kinetochore regulation during meiosis

Microtubule-kinetochore interactions during meiotic prophase are prevented in a variety of organisms ranging from budding yeast to mice. This regulation is essential for a meiosis-specific chromosome segregation pattern, without which chromosomes segregate as they would in mitosis (Miller et al., 2012). The mechanism whereby premature microtubule-kinetochore interactions are inhibited prior to meiosis I involves restricting the activity of cyclin-CDKs and disassembling the outer kinetochore, the subcomplex that mediates microtubule attachments.

The abundance of the essential outer kinetochore protein, Ndc80, declines in meiotic prophase (Miller et al., 2012; Meyer et al., 2015). Ndc80 is the defining member of a protein complex composed of Ndc80, Nuf2, Spc24 and Spc25, which form the microtubule-binding interface of the kinetochore. Recently, we found that Ndc80 is the limiting factor that dictates the timely dissociation and reassembly of the outer kinetochore during meiosis (Chen et al., 2017).

In addition to inhibition of Ndc80 protein synthesis through NDC80luti transcription (Chen et al., 2017; Chia et al., 2017), we propose that proteolytic mechanisms are in play to downregulate the preexisting pool of Ndc80 to fully inactivate kinetochore function. So far, we have identified both cis and trans determinants that regulate Ndc80 protein stability and kinetochore localization during meiotic prophase. Using a combination of approaches, we are investigating the mechanism of Ndc80 degradation and how this process affects kinetochore function in a broader context.